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Hyperthyroidism induces apoptosis in rat liver through activation of death receptor-mediated pathways

Ashok Kumar1, Rohit A Sinha, Meenakshi Tiwari

  • 1Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 014, India.

Journal of Hepatology
|February 27, 2007
PubMed
Abstract

Insights

Thyrotoxicosis induces liver cell death (apoptosis) by activating death receptor pathways, including the p75 neurotrophin receptor (p75NTR). This study reveals key molecular mechanisms underlying hyperthyroidism-related liver dysfunction.

Area of Science:

  • Hepatology
  • Endocrinology
  • Molecular Biology

Background:

  • Hepatic dysfunction in thyrotoxicosis lacks a clear molecular explanation.
  • Thyroid hormones significantly impact cellular processes, including cell death pathways in the liver.

Purpose of the Study:

  • To investigate the role of death receptor pathways, specifically p75 neurotrophin receptor (p75NTR), in the liver during hyperthyroidism.
  • To elucidate the molecular mechanisms of hepatic apoptosis induced by altered thyroid status.

Main Methods:

  • Hyperthyroidism was induced in Sprague-Dawley rats using triiodothyronine injections.
  • Apoptosis was assessed via TUNEL assay and caspase-3 activation.
  • Levels of death ligands, receptors, and downstream signaling molecules (caspase-8, p75NTR, NF-kappaB, JNK) were quantified.

Main Results:

  • Hyperthyroid rat livers exhibited significant apoptosis with elevated TNF-alpha, Fas ligand, TNF-receptor-1, Fas, and caspase-8 activation.
  • For the first time, elevated p75NTR and its ligands (pro-NGF, pro-BDNF) were observed in hyperthyroid rat livers, with p75NTR expressed on most apoptotic cells.
  • Triiodothyronine initially activated NF-kappaB, followed by deactivation and sustained JNK activation.

Conclusions:

  • Hyperthyroidism-induced hepatic apoptosis is mediated by death receptor pathways.
  • p75 neurotrophin receptor (p75NTR) activation is implicated in the liver pathology of thyrotoxicosis.

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